| Currently acquired immunodeficiency syndrome (AIDS) has become a serious infectious diseases against the health of all mankind. Highly active antiretroviral therapy (HAART) could suppress the human immunodeficiency virus-1 (HIV) replication, slow disease progression, it is the most effective method of control and treatment of AIDS up to now. Past results showed that specific cytotoxic T lymphocyte (CTL) play a key role in controlling HIV-1 replication, but research in this area is mainly aimed at those without HAART treatment of HIV-1 infection persons, and the relevant HAART on HIV-1-specific CTL immune response of the domestic and international studies have reported little , it's of great significance to study HAART for specific CTL immune responses in infected people for understanding the post-HAART immune function of the body's cells and explore the internal mechanism of immune reconstitution .Previous studies have clearly indicated HLA-I alleles influence HIV-1-specific CTL responses and disease progression, However, the results of these research datas are based on non-Chinese peoples , these aspects of research has not yet reported seeing in the domestic research. The different groups of people of their HLA-I allele frequencies show polymorphism, Chinese population distribution of HLA-I allele frequency was significantly different from other races. Therefore, It's essential to study China's population to HLA-I allele frequency and the correlation of specificity of CTL immune response. It can not only understand the relation between China infected with HIV-1 specific CTL response frequency and HLA-I polymorphism, but also can be found the specific HLA-I allele which impact HIV-1-specific CTL responses frequency and disease progression.This study chose China Guangdong area HIV-1 infected persons as the research object . Frequency of Interferon-γ(IFN-γ) secreting cells in PBMC from 16 untreated and 84 HAART-treated HIV-1-infected individuals were assessed by stimulation with a peptide pool containing 12 overlapping peptides in HIV-1 P24, by using assay of enzyme-linked immunospot (ELISPOT);and used PCR-SSP method tested HLA-I type allele of all persons infected. Research HAART and HLA-I type alleles on HIV-1-specific CTL immune response.Main research contents and the results are as follows:1. Detected 100 cases of HIV-1 infected antigen-specific CTL immune response levels we found,that 48 cases of infected persons CTL are able to recognize HIV-1 peptide epitopes in immune response, 52 cases of infected people do not recognize HIV-1 peptide epitope without immune responses, Response group CD4 + T cell counts was higher than the non-response group (P = 0.01).2. According to HAART treatment time, the HIV-1 infected persons were divided into untreated group, treatment time less than 12 months group and the treatment time more than 12 months group, compared with specific CTL immune response magnitude of these three groups we found that, Specific CTL immune response magnitude in more than 12 months of treatment group is obviously higher than that in less than that in 12 months of the treatment group and untreated group (P = 0.048; P = 0.027). Further these three groups of CD4+ T cells were detected was found ,the number of CD4+ cells in more than 12 months of treatment group is significantly greater than that in less than that in 12 months of the treatment group (P = 0.0003).3. According to CD4 + T cell counts, The HIV-1 infected persons were divided into CD4 + T cells <200/μL group, CD4 + T cell count 200 ~ 350/μL group, CD4+ T cell count> 350/μL Group. Positive response rate of HIV-1 specific CTL immune responses respectively were 19.4%(6/31), 61.8%(21/34) and 60.0%(21/35). Compare with these three group-specific CTL-positive response rate we found that specific CTL-positive response rate of CD4+ T cell count <200/μL group was significantly lower than those which in the CD4 + T cell count 200 ~ 350/μL, CD4+ T cell count > 350/μL group (P = 0.001; P = 0.001). Compared with specific CTL immune response magnitude of these three groups was found that CD4 + T cell count <200/μL group-specific CTL response magnitude was significantly lower than CD4 + T cell count 200 ~ 350/μL Group,CD4 + T cell count> 350/μL group (P = 0.0003; P = 0.009). Pairs of three groups of HIV-1 infected plasma viral load testing was found that the three groups of viral load were with a statistically significant difference (P = 0.005).In which CD4 + T cells <200/μL in HIV infection were significantly higher than the other two groups (P = 0.004; P = 0.009).4. All of the selected HIV-1 infected persons HLA-I alleles were detected we found , with different HLA-I alleles of HIV-1 infection had different response for the HIV-1 peptide epitopes of the immune response. HLA-A alleles in the highest positive response were the less common genotype (57.1%), followed by HLA-A * 33 (55.0%) and HLA-A * 11 (50.8%); HLA-B alleles in the highest positive response were HLA-B * 58 (61.9%), followed by HLA-B * 40 (54.2%) and the less common allele (53.8%); HLA-C allele, the positive response was followed by HLA-Cw07 (52.8%), HLA-Cw * 03 (50%), HLA-Cw * 01 (45%).5. Carrying HLA-B*18,-B*40 and-B*58 genotype infected antigen-specific CTL immune respond strongly among HIV-1 infected persons, especially HLA-B*18/B*40 heterozygotes; HLA-B * 58 genotype-specific CTL response magnitude and the positive response rate was significantly higher than HLA-B * 51 genotype (P = 0.041; P = 0.031).Though there was no distinction between Unusual expression of HLA-A alleles of those infected and Expression of HLA-A * 11,-A * 33 among those infected in specific CTL response magnitude and the positive response rate. CD4 + T cells count has statistically significance in among groups(P = 0.027; P = 0.019). Conclusion1. If we don't take the factor of HAART treatment into consideration, the higher of CD4+T counts, the stronger of HIV-1 antigen-specific CTL immune response in HIV-1 fection and CD4+T counts is positive correlated with HIV-1 antigen-specific CTL immune response.2. HAART therapy can enhance specific CTL immune response in HIV-1 infected patients. It will improve the specific CTL immune response to extend the treatment time to more than one year.3. There is strong specific CTL immune response in HIV-1 infected patients with lower viral load.4. The high frequency of HLA-I allele were HLA-A * 11 (0.59), HLA-A * 02 (0.53), HLA-Cw * 03 (0.50), HLA-Cw * 01 (0.40), HLA-B * 46 (0.35) in our study of HIV-1 infected persons. HLA-B allele is more complex and diverse than HLA-A, HLA-Cw allele.5. Specific CTL immune response seems to independent to the distributed frequency of HLA-A, B, Cw allele in HIV-1 infected individuals, there was significant difference of HIV-1 specific CTL immune responses with HLA-B genotypes individuals,while this phenomenon is not found in HLA-A and HLA-Cw genotyes. It showed that HLA-B allele is the most influence on HIV-1 specific CTL immune responses.6. HLA-B * 58, HLA-B * 40, HLA-B * 18 genotype could be HLA-I restriction sites, and we first found that specific CTL immune response may be more advantage to HIV-1 peptide epitope in HIV-1 infection patients with HLA-B * 40 / B * 18 heterozygous . |
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