Cord Blood Innate-like T cell responses in neonates born to healthy women and women living with HIV

David Rach¹Hao-Ting Hsu²Nginache Nampota-Nkomba^3,4Godfrey Mvula³Felix A. Mkandawire³Osward M. Nyirenda³Bernadette Hritzo¹Laura Cioetto Mazzabò⁵Giulia Degiacomi⁵Francesca Boldrin⁵Riccardo Manganelli⁵Andrea G. Buchwald⁶Franklin R. Toapanta⁶Marcelo B. Sztein⁶Miriam K. Laufer⁶Kirsten E. Lyke^6*Cristiana Cairo^2,7*

• ¹Molecular Microbiology and Immunology Graduate Program, University of Maryland School of Medicine, Baltimore, United States
• ²Institute of Human Virology, University of Maryland School of Medicine, Baltimore, United States
• ³Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
• ⁴Graduate Program in Life Sciences, University of Maryland School of Medicine, Baltimore, United States
• ⁵Department of Molecular Medicine, University of Padova, Padova, Italy
• ⁶Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, United States
• ⁷Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, United States

Innate-like T cells (ILT), including 𝛾𝛿 T cells (V𝛿2s), Natural Killer T cells (NKTs) and Mucosalassociated Invariant T cells (MAITs), integrate innate and adaptive immunity, playing important roles in homeostatic conditions as well as during infection or inflammation. ILT are present on both sides of the fetal-maternal interface, but our knowledge of their phenotypical and functional features in neonates is limited. Using spectral flow cytometry we characterized cord blood ILT in neonates born to healthy women and women living with HIV. We describe extensive phenotypic and functional heterogeneity within the cord V𝛿2 cells at baseline and following activation. In neonates born to women with HIV, we observed modest differences in ILT frequencies ex-vivo and altered proportions of V𝛿2 cells producing IFN𝛾+ or TNF𝛼+, both ex-vivo and after expansion, compared to HIV unexposed infants. Consistent with prior studies, infants born to mothers who initiated ART before pregnancy exhibited less immune perturbation overall. Herein we expand our knowledge of ILT at the maternal-fetal interface by a comprehensive phenotypic analysis of these rare subsets.