Cardiac morbidity in HIV infection is associated with checkpoint inhibitor LAG-3 on CD4 T cells

Suresh Pallikkuth, Rajendra Pahwa, Bagavathi Kausalya, Shanmugam Saravanan, Li Pan, R. Vignesh, Syed Iqbal, Sunil S. Solomon, Kailapuri G. Murugavel, Selvamuthu Poongulali, Nagalingeswaran Kumarasamy, Savita G Pahwa

Research output: Contribution to journalArticle

Abstract

Recent findings point to a role of Checkpoint Inhibitor (CPI) receptors at the tissue level in immune homeostasis. Here we investigated the role of CPI molecules on immune cells in relation to cardiac function. Participants recruited in Chennai, India consisted of HIV+ ART naive viremic (Gp1 n = 102), HIV+ on ART, virologically suppressed (Gp2, n = 172) and HIV negative healthy controls (Gp3, n = 64). A cross-sectional analysis of cardiac function, arterial resistance and immunologic assessment of CPI expressing T cells was performed. Data indicate that ART naive exhibited cardiac function impairment and greater arterial stiffness than the other groups. Frequencies of CD4+ T cells expressing LAG-3 and PD1 were higher in ART naïve while TIGIT and TIM3 were similar among the patient groups. LAG-3+, PD1+ and dual LAG-3+PD1+ CD4 T cells were inversely correlated with cardiac function and arterial elasticity and directly with arterial stiffness in ART naïve participants and with arterial elasticity in virally suppressed group on ART. We conclude that HIV induced upregulation of LAG-3 singly or in combination with PD1 in immune cells may regulate cardiac health and warrant mechanistic investigations. The implications of these findings have bearing for the potential utility of anti-LAG-3 immunotherapy for cardiac dysfunction in chronic HIV infection.

Original languageEnglish (US)
Pages (from-to)e0206256
JournalPLoS One
Volume13
Issue number10
DOIs
StatePublished - Jan 1 2018

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T-cells
HIV infections
cardiac output
HIV Infections
morbidity
T-lymphocytes
HIV
Morbidity
T-Lymphocytes
Vascular Stiffness
Elasticity
elasticity (mechanics)
Bearings (structural)
Stiffness
immunotherapy
cross-sectional studies
Immunotherapy
India
homeostasis
Homeostasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Cardiac morbidity in HIV infection is associated with checkpoint inhibitor LAG-3 on CD4 T cells. / Pallikkuth, Suresh; Pahwa, Rajendra; Kausalya, Bagavathi; Saravanan, Shanmugam; Pan, Li; Vignesh, R.; Iqbal, Syed; Solomon, Sunil S.; Murugavel, Kailapuri G.; Poongulali, Selvamuthu; Kumarasamy, Nagalingeswaran; Pahwa, Savita G.

In: PLoS One, Vol. 13, No. 10, 01.01.2018, p. e0206256.

Research output: Contribution to journalArticle

Pallikkuth, S, Pahwa, R, Kausalya, B, Saravanan, S, Pan, L, Vignesh, R, Iqbal, S, Solomon, SS, Murugavel, KG, Poongulali, S, Kumarasamy, N & Pahwa, SG 2018, 'Cardiac morbidity in HIV infection is associated with checkpoint inhibitor LAG-3 on CD4 T cells', PLoS One, vol. 13, no. 10, pp. e0206256. https://doi.org/10.1371/journal.pone.0206256
Pallikkuth, Suresh ; Pahwa, Rajendra ; Kausalya, Bagavathi ; Saravanan, Shanmugam ; Pan, Li ; Vignesh, R. ; Iqbal, Syed ; Solomon, Sunil S. ; Murugavel, Kailapuri G. ; Poongulali, Selvamuthu ; Kumarasamy, Nagalingeswaran ; Pahwa, Savita G. / Cardiac morbidity in HIV infection is associated with checkpoint inhibitor LAG-3 on CD4 T cells. In: PLoS One. 2018 ; Vol. 13, No. 10. pp. e0206256.
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