Mucosal associated invariant T (MAIT) cell dynamics during acute HIV-1 infection — ASN Events

Mucosal associated invariant T (MAIT) cell dynamics during acute HIV-1 infection (#183)

Kerri G. Lal 1 2 3 , Edwin Leeansyah 1 4 , Joana Dias 1 , Matthew Creegan 2 3 , Margaret C. Costanzo 2 3 , Leigh Anne Eller 2 3 , Shelly Krebs 2 3 , Hannah Kibuuka 5 , Lucas Maganga 6 , Sorachai Nitayapan 7 , Fredrick Sawe 2 8 , Julie Ake 2 , Nelson L. Michael 2 , Merlin L. Robb 2 3 , Michael A. Eller 2 3 , Johan K. Sandberg 1
  1. Medicine, Karolinska Institutet, Stockholm, Sweden
  2. U.S. Military HIV Research Program, Silver Spring, MD, USA
  3. Henry M. Jackson Foundation, Bethesda, MD, USA
  4. Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169587, Singapore
  5. Makerere University Walter Reed Project, Kampala, Uganda
  6. Walter Reed Program- Tanzania, Mbeya, Tanzania
  7. Royal Thai Army Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
  8. Kenya Medical Research Institute/Walter Reed Project, Kericho, Kenya

In chronic HIV-1 infection, MAIT cells are lower in frequency, have increased expression of activation markers, and are less functional compared to healthy controls. The temporal dynamics of MAIT cell loss and dysfunction in HIV-1 infection is not known. To better understand MAIT cell dynamics in early HIV-1 infection, cryopreserved PBMC from 20 donors followed from pre-infection through early acute infection were studied for changes in MAIT cell frequency, phenotype, and function prior to infection and at 3 time points out to 3 months post-infection. Donor PBMC were from women in East Africa and men in Thailand. Baseline pre-infection frequencies of MAIT cells differed between the two regions at pre-infection, with East Africans having lower baseline frequencies of MAIT cells compared to Thais (median=0.737% and 1.93% of CD3+ T cells, respectively). Surprisingly, MAIT cell frequencies did not change significantly during acute HIV-1 infection compared to pre-infection. However, MAIT cells showed an increased expression of activation markers CD38, HLA-DR, PD-1, and TIGIT at peak viral load (median 16 days since first positive test for HIV-1 RNA), and remained elevated three months post-infection (median 84.5 days since first positive test for HIV-1 RNA). Expression of CD38 and HLA-DR correlate positively with plasma levels of sCD14 (r=0.727 and r=0.807, respectively), a marker of monocyte activation and microbial translocation. Functionally, MAIT cells displayed reduced production of TNFα and IFNγ after in vitro stimulation with PMA/ionomycin at the 3 months post-infection time point compared to pre-infection. Together, these data are consistent with a model where MAIT cells become highly activated early in HIV-1 infection, possibly due to translocation of microbial products across a compromised gut barrier. In this model, chronic exposure to antigen may lead to activation-induced cell death and slow progressive decline in MAIT cell frequency and functionality over time.