Abstract
HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.
Original language | English (US) |
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Pages (from-to) | 5803-12 |
Number of pages | 10 |
Journal | Blood |
Volume | 118 |
Issue number | 22 |
DOIs | |
State | Published - Nov 24 2011 |
Externally published | Yes |
Keywords
- Animals
- B-Lymphocytes/drug effects
- CD4-Positive T-Lymphocytes/immunology
- Immunization, Secondary
- Leishmania major/immunology
- Leishmaniasis Vaccines/administration & dosage
- Leishmaniasis, Cutaneous/prevention & control
- Lymph Nodes/immunology
- Lymphocyte Activation/drug effects
- Macaca mulatta/immunology
- Simian Acquired Immunodeficiency Syndrome/immunology
- Simian Immunodeficiency Virus/immunology
- T-Lymphocytes/drug effects
- Vaccination/methods
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Intramural